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4 does not predict mortality, cognitive decline, or dementia in the oldest old
From the Departments of Clinical Neurosciences (Drs. Juva and Verkkoniemi), Pathology (Dr. Polvikoski), and Medicine (Drs. Kainulainen and Kontula), Helsinki University Central Hospital, University of Helsinki; the Department of Public Health Science and General Practice (Dr. Viramo), University of Oulu, and Unit of General Practice, Oulu University Hospital; and the Department of Public Health and General Practice and Department of Medicine (Dr. Sulkava), University of Kuopio, Finland.
Address correspondence and reprint requests to Dr. Kati Juva, Valhallankatu 16 A 17, 00250 Helsinki, Finland; e-mail: katijuva{at}katto.kaapeli.fi
OBJECTIVE: To examine the effect of the 
4 allele on cognitive decline in the oldest old.
METHODS: We studied all 601 citizens of the city of Vantaa age 85 years and older in 1991. A total of 553 subjects (92%) took part in the study, which used the Mini-Mental State Examination (MMSE) and assessment of dementia according to the Diagnostic and Statistical Manual of Mental Disorders, third ed., revised (DSM-III-R) criteria. The survivors were re-examined 3 years later. APOE genotype was determined in 510 subjects, representing 83.2% of the original population.
RESULTS: Approximately one-half of the subjects (n = 250) died before the follow-up, and 253 subjects (97.3% of the survivors) were re-examined. The occurrence of the APOE 4 allele did not have any significant effect on survival. Of the 187 previously nondemented subjects, 58 (31%) had developed dementia. The OR for the 4 carriers to develop dementia was not significant: OR = 1.78; 95% CI = 0.88 to 3.60. In individuals with a follow-up MMSE score (n = 222), the mean decline in the score was 3.1 points. APOE 4 carrier status did not have a significant effect on the mean MMSE change except in the previously demented subjects, among whom the drop was larger in the APOE 4 carriers.
CONCLUSIONS: The lack of association between APOE 4 carrier status and mortality, or development of dementia, or cognitive decline in these very elderly people, whether analyzed in the whole population or among the nondemented subjects only, suggests that the APOE 4 effect in younger subjects is age-dependent, and that it is no longer present in very old age.
Key words: APOE—Dementia—Mortality
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